Repurposing of Macrolide Antibiotic Clarithromycin for the Prevention of Lung and Breast Cancer

克拉霉素（CAM）是一种广谱大环内酯类抗生素，用于治疗皮肤、软组织和呼吸道的细菌感染；治疗和预防人类免疫缺陷病毒感染者的播散性禽分枝杆菌复合感染；并根除引起溃疡的胃幽门螺杆菌感染。它是低成本的，口服生物可利用的，并且具有低毒性，即使以200毫克/天的剂量给药4年。

Clarithromycin (CAM) is a broad-spectrum macrolide antibiotic used to treat bacterial infections of the skin, soft tissue, and respiratory tract; to treat and prevent disseminated Mycobacterium avium complex infections in people with human immunodeficiency virus; and to eradicate ulcer-causing gastric Helicobacter pylori infections. It is low-cost, orally bioavailable, and has a low toxicity profile, even when administered for 4 years at a dose of 200 mg/day. Due to its strong anti-inflammatory, immunomodulatory, and anti-angiogenic properties, including the suppression of NFκB, the expansion of anti-tumor natural killer T cell subsets, and the reduction of VEGF, CAM has been identified as one of the most promising candidates for repurposing as an anti-cancer drug. In the clinical setting, it completely regressed high-grade gastric B-cell lymphoma, and showed efficacy in the treatment of naïve and refractory multiple myeloma when combined with other immunomodulatory drugs. In light of this, there are numerous ongoing clinical trials testing the efficacy of CAM in the prevention and treatment of gastric cancer, MALT, and other B-cell lymphomas. The purpose of this Task Order is to test the efficacy of CAM in the prevention of breast and lung cancer. CAM has been shown to increase the overall survival of rats and mice inoculated subcutaneously with mammary adenocarcinoma and Lewis lung carcinoma (LLC) cells, respectively, and to reduce the number of tumor nodules in the lungs of mice intravenously injected with LLC cells. In a prospective study, CAM has also been shown to significantly increase the overall survival of patients with advanced non-small cell lung cancer, extending their lives from 277 to 535 days.